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Identifying Mechanisms Of Resistance And Potential Therapeutic Targets For Pediatric Acute Myeloid Leukemia, John Timothy Caldwell

Wayne State University Dissertations

Acute myeloid leukemia (AML) is a potentially devastating disease that can affect people of all ages. While there are certain patient groups that typically have favorable outcomes, in the pediatric population, overall survival (OS) is approximately 70%, leaving much progress to be made. Children with Down syndrome (DS) have a substantially elevated risk for developing AML, especially of the megakaryocytic phenotype (AMKL).

Patients with DS AMKL almost universally harbor a mutation in the gene encoding the GATA1 transcription factor, resulting in the translation of a short-form protein GATA1s, which has been shown to contribute to chemotherapy sensitivity. In contrast, in …